The OBR Blog

February 21, 2013 - 09:02 am Posted in Featured comments0 Comments

Specialty pharmacy offers drug manufacturers important solutions for self-administered oncology drugs. With the increased use of the specialty pharmacy channel, specialty pharmacies are becoming a norm for standard operating procedures. For instance, all of the oral oncology products launched in 2011 and 2012 are distributed through specialty pharmacies. A number of factors are driving this trend, including:

  • Increased high-cost specialty product volume, especially oral oncolytics;
  • Pipeline shifts to oral specialty products presaging future marketed specialty drug growth;
  • Growing physician acceptance of orals;
  • Manufacturer desire to improve safety, supply chain control and patient access;
  • Payer demand to control specialty spend and improve adherence and compliance

According to EvaluatePharma, in 2016, seven of the top 10 best-selling drugs (by revenue) are projected to be specialty drugs compared with three in 2010. Physicians have become more willing to prescribe oral oncology therapies despite there being no financial incentive to their practice—in part, because of the services offered by specialty pharmacies.

Manufacturers use specialty pharmacies to gain greater control over the supply chain, and provide the clinical care or training—with oncology expertise—that the patient may not otherwise receive.

Payers have also identified specialty pharmacies as an important part of care for patients and at the same time controlling specialty spend. Payers also may be restrictive in which specialty pharmacy their members can access.

At least 18 months before launch, manufacturers may want to begin to incorporate a channel strategy into their commercialization plans since it is necessary to understand the opportunities and risks of strategic options in choosing channel partners.

Factors for manufacturer’s to consider when determining a specialty pharmacy network include:

  • Distribution control versus patient access trade-offs (fewer specialty pharmacies allow for greater control, but may cause access issues; larger networks may result in problems trying to coordinate all specialty pharmacies so patients get a consistent experience), which should factor in drug characteristics (safety issues, administration complexity, cost) and patient population size
  • Desired practice and manufacturer services. Hub services can be helpful in alleviating practice burden, and specialty pharmacies may provide valuable market data as part of their contract.
  • A limited strategy for large patient populations could result in a bottleneck for obtaining the drug and cause issues with higher patient cost-sharing due to distribution through non-payer-preferred specialty pharmacies, while a very limited distribution strategy may be warranted for drugs with very small patient populations, although these may require programs and policies in place to ensure access and financial support for patients with non-overlapping manufacturer and payer specialty pharmacy networks.
  • Access to market data is also important for manufacturers, as specialty pharmacies do not regularly report this information to data aggregators. Establishing data submission as part of an SP contract or working with hub services is important in order to know how a product is being used and to identify issues and opportunities.

The key to success when engaging a specialty pharmacy is to ensure that the specialty pharmacy is effective, efficient, and experienced in oncology—requiring nominal paperwork, avoiding redundant or unnecessary administrative steps, and offering expert-level clinical oncology support. Overall, the specialty pharmacy must be reliable and easy for oncology patients and oncologists to use lest they also become a barrier to what they promise to bring, optimal access to complex and costly medications.

By: Deni Deasy Boekell, Senior Director, Commercial Planning, Kantar Health

This blog is an excerpt from a full length article featured in the February issue of OBR green. You can visit the full length article here:

The-Evolving-Dynamics-of-Specialty-Pharmacy-in-Oncology.

February 15, 2013 - 09:02 am Posted in ASCO GU Conference Coverage comments0 Comments

In recent years the field of prostate cancer has undergone significant evolution with the introduction of newer, better-tolerated treatment options. The introduction of the first therapeutic cancer vaccine (Provenge, Dendreon) sparked the idea of treating metastatic castrate-resistant prostate cancer (mCRPC) patients who weren’t symptomatic. This was followed by the advent of novel hormonal therapies being used in the post-chemotherapy setting, which challenged the previous notion that these patients were hormone-insensitive. Most recently, we’re witnessing the influx of these novel hormonal therapies into the pre-chemotherapy setting. However, one area that has remained stable over the years is the treatment paradigm for newly symptomatic mCRPC. The TAX327 trial was key in establishing docetaxel plus prednisone as the “gold standard” for patients with mCRPC. For nearly a decade it’s been a foregone conclusion that docetaxel is the best treatment option for these patients, and to improve upon outcomes in the first-line setting we need to develop new regimens that build on the docetaxel foundation. In the era of targeted therapy, it’s not surprising that several targeted agents have been investigated to explore additive benefits to this regimen with the goal of improving survival beyond the 19 months that the docetaxel/prednisone regimen offers (Tannock, 2004). However, it is saddening to observe that front-line mCRPC has become a graveyard for novel therapies, including atrasentan (AstraZeneca), Avastin® (bevacizumab, Roche/Genentech/Chugai), Revlimid® (lenalidomide, Celgene), Zaltrap® (ziv-aflibercept, Regeneron/Sanofi), and zibotentan (ZD4054, AstraZeneca). Each of these drugs demonstrated early promise of activity, but each has attempted and failed to improve upon the bar that docetaxel set for overall survival. Now one more promising targeted agent has met with the same fate: Sprycel® (dasatinib, Bristol-Myers Squibb). The results from the pivotal READY trial were reported Thursday at the American Society of Clinical Oncology (ASCO) Genitourinary Cancer Symposium in Orlando, Florida.

The trial (NCT00744497) evaluated whether Sprycel improved survival when added to the docetaxel/prednisone regimen as first-line therapy in mCRPC patients. The study accrued 1,522 patients who were randomized 1:1 to Sprycel/docetaxel/prednisone or docetaxel/prednisone. Disappointingly, the study failed to achieve an improvement in median overall survival (mOS): the curves for the two arms were overlapping (mOS 21.2 months in placebo/docetaxel arm versus 21.5 months in Sprycel/docetaxel/prednisone arm; HR 0.99, p=0.9009). Subset analysis by age, EGOG status, bone metastasis or PSA progression also failed to demonstrate any difference in mOS between the two arms. There was no difference in median progression-free survival (mPFS) in the Sprycel/docetaxel/prednisone arm versus placebo/docetaxel/prednisone arm (11.8 versus 11.1 months; HR 0.92, p=0.2164). A modest delay in skeletal-related events was observed in the Sprycel arm, which was not entirely surprising considering the Src relation to osteoclasts.

The efficacy of placebo/docetaxel/prednisone arm in the READY trial is strikingly similar to that observed in the placebo/docetaxel/prednisone arm from the Zaltrap pivotal trial (VENICE) (Tannock, Abstract 13, ASCO GI 2013). The VENICE trial was previously reported to have failed via press release, but this was the first time that complete data was reported. In the VENICE trial, Zaltrap plus docetaxel/prednisone achieved a mOS of 22.1 months, which was not significantly different (p=0.38) compared to 21.2 months mOS in the placebo/docetaxel/prednisone arms. There were no differences in mPFS or PSA responses between the Zaltrap/docetaxel/prednisone and placebo/docetaxel/prednisone arms (mPFS: 6.9 versus 6.2 months; PSA: 68.6% versus 63.5%). Additionally, Zaltrap added some toxicities, including gastrointestinal perforations, hypertension, infections and respiratory disorders, that led to shorter duration of treatment.

Mechanistically (Src kinase inhibition) and preclinical studies (synergism with docetaxel) laid a very solid foundation for the investigation of Sprycel in prostate cancer. However, the transition for Sprycel into clinics was based on mediocre Phase I/II results. In that study, the addition of Sprycel to docetaxel demonstrated an improvement in partial tumor response (60%) and superior PSA decline (57%) when compared with historical controls (Araujo, Cancer 2012, 118: 63-21). The biggest criticism of the READY trial was launch of a large, 1,500-patient Phase III trial on the basis of efficacy observed in a single-arm (less than 50 patients) Phase II study with no clear PFS or survival benefit. The caveats of comparing single-arm studies with historical data becomes more apparent when comparing the differences in OS benefit of the control arms in the READY and VENICE pivotal trials (mOS: 21.2 months) with that observed in the TAX327 trial (mOS: 19.2 months).

Is there any hope left for targeted therapies or novel chemotherapies hoping to improve upon the activity of docetaxel in first-line mCRPC? A quick review of history (eight failed agents) and current landscape (two in pivotal trials) might suggest “Very Slim.” Currently two agents are in pivotal clinical trials for chemotherapy-naïve symptomatic mCRPC. Custirsen (OGX-011, Oncogenex/Teva) is an antisense oligonucleotide that is currently in a Phase III trial (SYNERGY) in combination with docetaxel/prednisone versus docetaxel/prednisone. The primary endpoint is OS, and the trial is expected to report results by the end of 2013. The pivotal trial was initiated based on data from a randomized Phase II trial in which custirsen/docetaxel/prednisone failed to achieve the primary endpoint of improved PSA decline rate or improved response rate. However, custirsen/docetaxel/prednisone improved OS (23.8 months versus 16.9 months), and a trend to improved PFS was observed (7.3 versus 6.1 months) compared to docetaxel/prednisone. With the caveat of cross-trial comparison, the efficacy of the placebo arm in this Phase II trial compares closely to that from TAK327 trial but is much lower than that observed with docetaxel-alone arms in the VENICE and READY trials, leading to some concerns that SYNERGY could meet with the same fate.

The other agent in a pivotal trial in this setting is Jevtana® (cabazitaxel, Sanofi), which is a taxane derivative that is currently approved for docetaxel-pretreated mCRPC patients. Jevtana is being investigated in the Phase III FIRSTANA trial, comparing docetaxel plus prednisone versus Jevtana plus prednisone in first-line mCRPC. The endpoint of this trial is OS, and the trial will report by the end of 2013. To date, Jevtana has not been explored in a head-to-head trial with docetaxel, and the only available results are from docetaxel-refractory patients, where Jevtana/prednisone achieved mOS of 15.1 months and mPFS of 2.8 months (deBono, Lancet 2010; 1147-1154). It would be interesting to see whether Jevtana will be able to demonstrate superiority to docetaxel in the front-line setting and manage to maintain a decent toxicity profile with few discontinuations due to toxicity.

The mCRPC market appears to be on a trajectory toward a relinquishment to novel hormonal agents and a regression of chemotherapy and other targeted therapies to later lines. If Jevtana manages to supersede docetaxel, it may only be a marginal improvement in this field, with a swap of one taxane for another. As the only targeted agent left in late-stage development seeking to improve upon the efficacy of docetaxel, custirsen could be the only hope left to rejuvenate interest in targeted therapy plus chemotherapy combinations, keeping alive the complex interplay between hormones and chemotherapy in the management of mCRPC.

By: Neesha Suvarna, PhD, Consultant, Kantar Health

February 12, 2013 - 10:02 pm Posted in Featured comments0 Comments

ORLANDO, FL – Three studies with implications for managing patients with prostate cancer and kidney cancer were featured at a pre-meeting Presscast of the 2013 Genitourinary Cancers Symposium sponsored by ASCO, ASTRO, and SUO. The main findings of the respective studies are:

  • Prostate cancer found in African-American men and older men is more likely to be high-risk disease.
  • Men with high-risk prostate cancer treated with radiation plus anti-androgen therapy can be safely treated with 18 months of androgen blockade instead of 24 – 36 months.
  • Elderly patients with small kidney masses have similar cancer-related survival with surveillance versus surgical resection.

High-Risk Prostate Cancer

About 40% of cases of high-risk, PSA-detected prostate cancer occur in men over the age of 75 years, and elderly men are 9.4 times more likely than men under the age of 50 to be high risk. African-American men of any age are more likely than white men to have high-risk disease. These findings of a large, population-based, retrospective study are among the first to suggest that PSA testing can identify high-risk prostate cancer.

Early, asymptomatic prostate cancer is not detectable on physical exam. The study suggests that PSA testing may be warranted in elderly and African-American men, but more research is needed to show that early detection and treatment can improve outcomes.

“If we stop PSA screening altogether [as recommended by the U.S. Preventive Services Task Force], there is no other method to detect this form of prostate cancer sufficiently early to have the best chance of helping this group of high-risk patients. The findings of this study will help physicians and certain patients make more informed decisions on whether or not they want to proceed with PSA testing, although more research (and longer follow-up) is needed to determine the effects of early detection and intervention on outcome in these high-risk patients,” stated lead author Hong Zhang, MD, PhD, University of Rochester, Rochester, NY.

The study used SEER data to identify 70,345 men with early-stage (T1C), node-negative, prostate cancer diagnosed between 2004 and 2008. The investigators determined the probability of developing low-, intermediate-, and high-risk prostate cancer based on PSA criteria and Gleason stage.  Low risk was defined as PSA < 10 mg/L and Gleason score of 6 or lower; intermediate risk was defined as PSA 10-20 mg/L and/or Gleason 7; and high-risk disease was defined as PSA of 20 or higher mg/L and/or Gleason score of 8 or higher; 47.6% were found to have low-risk disease; 35.9% intermediate-risk, and 16.5%, high-risk.

Men over the age of 75 accounted for 11.8% of this population, but comprised 24.3% of intermediate- and 26.1% of high-risk disease.

Shortened Duration of Hormone Therapy for High-Risk Prostate Cancer

Patients with high-risk prostate cancer treated with radiation had similar survival with 18 months of hormone therapy compared with 36 months of hormone therapy, according to results of a randomized Phase III study.

Given the compromising effects of hormone therapy on quality of life, “shorter-term hormone therapy could have a big impact on the lives of men with prostate cancer, reducing the quantity and intensity of its unpleasant side effects as well as treatment costs. We hope these results will convince doctors that they can stop hormone therapy after 1.5 years instead of 2 to 3 years,” stated lead author Abdenour Nabid, MD, Centre Hospitalier de Universitaire de Sherbrooke in Sherbrooke, Canada.

The optimal duration of androgen ablation therapy in high-risk prostate cancer remains in question. The study randomized 630 patients with node-negative, high-risk prostate cancer to radiotherapy to the pelvic area and prostate bed plus 18 months of androgen ablation therapy versus 36 months of androgen ablation therapy (biculatamide 1 month plus goserelin every 3 months).

Demographic and disease characteristics of the study population were well balanced between the two arms. Median age was 71 years, median PSA was > 20/ng/ml, and median Gleason score was > 7.  Most patients had stage T3 or T4 disease.

At a median follow-up of 77 months, no difference in mortality was found between the two-arms:22.9% in the shorter-duration hormone therapy arm versus 23.8% in the longer-duration arm. Of these deaths, 116 patients died of causes other than prostate cancer.

At 5 years, overall survival rates were 92.1% versus 86.8% for the 2 arms, respectively, and 10-year survival rates were 63.6% versus 63.2%, respectively. Disease-specific survival rates at 5 years were 97.6% versus 96.4%, respectively, and 10-year disease-specific survival rates were 87.2% in both arms.

Small Renal Masses in Elderly Can Be Managed by Surveillance

Small kidney masses identified in elderly patients can be safely managed by surveillance, avoiding the need for surgical resection.

A retrospective analysis of more than 8300 elderly patients with small kidney masses showed that kidney cancer-specific mortality was comparable with surveillance or surgical resection of the masses. Moreover, the study found that patients managed with surveillance had a lower risk of cardiovascular complications and death from all causes.

“Our analysis indicates that physicians can comfortably tell an elderly patient, especially a patient that is not healthy enough to tolerate anesthesia and surgery, that the likelihood of dying of kidney cancer is low and that kidney surgery is unlikely to extend their lives. However, since it is difficult to identify which tumors will become lethal, elderly patients who are completely healthy and have an extended life expectancy, may opt for surgery,” stated lead author William C. Huang, MD, New York University Medical Center, New York City.

The study was based on SEER registry data linked to Medicare claims for patients aged 66 or older diagnosed with small renal masses (i.e., under 1.5 inches in diameter). Of 8317 patients, 5706 (70%) underwent surgery and 2611 (31%) underwent surveillance. At a median follow-up of 4.8 years, 2078 deaths were reported (25% of the population); 277 deaths (3%) were due to kidney cancer.  The rate of kidney cancer-specific death was similar between the surveillance and surgery groups.

After controlling for patient and disease characteristics, patients who had surveillance had a significantly lower risk of death from any cause as well as a lower risk of a cardiovascular event.

The authors conclude that surveillance with modern imaging techniques is a safe option for management of small renal masses in elderly patients.

by Alice Goodman

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